miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1.
miR-205-5p inhibits homocysteine-induced pulmonary microvascular endothelium dysfunction by targeting FOXO1.
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miR-205-5p通过靶向FOXO1抑制同型半胱氨酸诱导的肺微血管内皮功能障碍。
DOI：
10.3724/abbs.2023127
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发表时间：
2023-07-25
影响因子：
3.7
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Huang X;Li Z;Zhang L;Yang Y;Wang Y;Li S;Li G;Feng H;Yang X
同型半胱氨酸（Hcy）是多种慢性疾病的危险因素，血管内皮细胞损伤被认为是这一过程的起始步骤。mirna参与了hcy诱导的内皮功能障碍，而mirna在同型半胱氨酸诱导的肺内皮功能障碍中的潜在机制和作用尚不清楚。在这里，我们发现miR-205-5p通过靶向CBS +/ -小鼠的FOXO1来减轻肺内皮功能障碍，以保护hcy诱导的肺内皮功能障碍。在机制上，我们发现Hcy可以导致miR-205-5p启动子的DNA超甲基化，因为DNMT1与其启动子的结合增加，这有助于降低miR-205-5p的表达。总之，miR-205-5p启动子高甲基化导致miR-205-5p表达下调，导致同型半胱氨酸诱导的肺内皮功能障碍期间miR-205-5p与fox01结合减少。我们的数据表明，miR-205-5p可能是对抗hcy诱导的肺损伤的潜在治疗靶点。
Homocysteine (Hcy) is a risk factor for multiple chronic diseases, and vascular endothelial cell injury has been regarded as the initiating step for this process. miRNAs are involved in Hcy-induced endothelial dysfunction, while the underlying mechanism and roles of miRNAs in pulmonary endothelial dysfunction induced by homocysteine are unknown. Here, we find that miR-205-5p alleviates pulmonary endothelial dysfunction by targeting FOXO1 in CBS +/‒ mice to protect against Hcy-induced pulmonary endothelial dysfunction. Mechanistically, we show that Hcy can lead to DNA hypermethylation of the miR-205-5p promoter due to the increased binding of DNMT1 to its promoter, which contributes to reduction of miR-205-5p expression. In summary, miR-205-5p promoter hypermethylation causes downregulation of miR-205-5p expression, resulting in a reduction in miR-205-5p binding to FOXO1 during homocysteine-induced pulmonary endothelial dysfunction. Our data indicate that miR-205-5p may be a potential therapeutic target against Hcy-induced pulmonary injury.
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